Although chronic rhinosinusitis (CRS) is a widespread disease affecting ˜15% of the US population, the pathogenesis is poorly understood. One of the most severe forms is CRS with hyperplastic sinonasal polyposis (CRSwNP). The presence of hyperplastic polyps in the sinuses is an ominous clinical feature signifying the presence of recalcitrant disease for which there is no known effective lasting treatment. Mucosal hyperplasia, a hallmark of the tissue remodeling observed in CRSwNP, results in chronic disease that becomes refractory to either medical or surgical management. Despite the significant morbidity of recurrent disease, central mechanisms regarding the pathogenesis of sinonasal polyposis remain poorly understood. Histological features of CRSwNP resemble that of asthmatic airways with endstage polyps displaying signs of Th2 inflammation characterized by infiltration with eosinophils, thickening of the basement membrane and hyperplasia of the epithelium and are strikingly reminiscent of the histopathology of severe asthmatic airways. Therefore, understanding factors controlling aberrant epithelial cell growth may provide critical insights into therapeutic strategies in the treatment of chronic rhinosinusitis with nasal polyposis, as well as asthma.
Despite the fact that epithelial hyperplasia is a key feature of sinonasal polyps, there is a surprising paucity of literature on studies of growth factors in the pathogenesis of epithelial hyperplasia in sinonasal polyps. Growth factors implicated in remodeling of asthmatic airways such as transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) were found to be increased in nasal polyp tissue. Messenger RNA for TGFβ1 and FGF are increased in tissue homogenates of polyps. Immunohistochemical analysis localized TGFβ1 to the extracellular matrix and stroma of nasal polyps, where eosinophils reside. There have been many studies of other selected growth factors in nasal polyposis, such as insulin-like growth factor (IGF), FGF, PDGF, and TGF beta. However, the effects of TGF and FGF on sinus tissue remodeling have not been established. Epidermal growth factor (EGF) is thought to play a key role in epithelial proliferation, growth and repair in asthma. EGF receptor over expression in bronchial epithelial cells has been found to correlate with asthma severity and steroid refractoriness. However the role of EGF in development of sinonasal polyps has not been explored.
VEGF (vascular endothelial cell growth factor) as an endothelial cell mitogen has been implicated in the development of nasal polyps. Immunohistochemical analysis of nasal polyps from children showed increased VEGF staining within the vascular endothelium and increased mean blood vessel count both of which correlated with size of nasal polyps. Others have also shown that enhanced VEGF and its receptor expression were localized to the endothelium, the basement membranes, perivascular spaces, and epithelium of polyps. These studies indicate that the epithelium is a significant, but not necessarily the sole, source of VEGF in polyp tissue; but they do not show if the VEGF found in the epithelium was produced in those cells or whether it was actually generated by endothelial cells. Moreover, there have been no investigations to date on the role of VEGF as an epithelial mitogen in sinus disease.